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Study: Electroshock therapy more successful for depression than ketamine

today.uconn.edu

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Re: Study: Electroshock therapy more successful for depression than ketamine

#71
post #65
post #48

Earlier quoted context omitted.

Curious what you mean by “particle level”? Like simulating every molecule in the body?

At this time, I mean every hormone and protein flowing in the bloodstream, along with the state of every single cell. Essentially, enough detail to get a list of symptoms and bodily sensations, and predict the outcome of any potential blood test or urinalysis. Or, alternatively, enough detail to take the results of a blood test/urinalysis, and predict the state of every single tissue in the body.

This is one of those hard problems in computing and medicine. Accurately simulating a neuron, for example, or other cells is beyond our capabilities. We have a difficult time even simulating individual receptors themselves on cells, which includes accurately predicting and simulating ligand binding on proteins.

Re: Study: Electroshock therapy more successful for depression than ketamine

#72
post #41

Earlier quoted context omitted.

Interesting information... it prompted me to do more research. According to wikipedia, Vitamin B-9 is broken down by our bodies into a family of compounds called "THF", which: 1. Help synthesize DNA, 2. Help repair/modify DNA, 3. Help create the amino acid "Methionine", which is a precursor to other amino acids, and is thus important for the synthesis of many proteins inside the body, 4. Activate Vitamin B12. A defic…

If you ever want someone else to work with you on that, I atleast would be very interested

... and my axe!

Re: Study: Electroshock therapy more successful for depression than ketamine

#73
post #41
post #23

My friend figured out for herself, when she was in her 30's, that she's a poor methylator who can't turn the food fortification folic acid into a usable form of Vitamin B-9. She once told me that adding L-Methylfolate to her routine was like flipping a switch from "depressed" to "not-depressed". But the doctors had already decided she was being "stabilized" by the anti-psychotic prescriptions they forced on her, so t…

Interesting information... it prompted me to do more research. According to wikipedia, Vitamin B-9 is broken down by our bodies into a family of compounds called "THF", which: 1. Help synthesize DNA, 2. Help repair/modify DNA, 3. Help create the amino acid "Methionine", which is a precursor to other amino acids, and is thus important for the synthesis of many proteins inside the body, 4. Activate Vitamin B12. A defic…

> One of these days, when I have enough free time, I want to develop a particle-level simulation of the human body, so that medical students, doctors, and curious laymen can see these processes in action on their personal computers.

Likely you wouldn't need/want a particle level simulation, but a kinetics level model. Just with kinetics you could draw simulations of "particle concentrations" or other fun things to show medical students, etc, but without the need to simulate the actual chemicals. Though eventually hopefully we could do that too! The AlphaFold breakthrough is a huge advance toward that IMHO.

> If I combine that with an affordable at-home blood test/diagnostic system, we will have a mechanism to bring affordable healthcare to every single person in the country. And perhaps a reliable method to find the true cause of a patient's depression, before prescribing them SSRI's or other psychiatric drugs.

Just getting all the kinetics together would be amazing. You could essentially do what you're talking about of calculating most likely causes (not just correlations). Though brain chemistry != entirety of depression or whatnot. Still just getting even the top 20 chemical cycles mapped from blood tests could be pretty awesome and help bring light to a huge range of conditions.

In my opinion, medicine currently is at a 1.0-1.5 order effects level. As in we can diagnose first order ailments pretty well. But second order effects? Not really, though I said 1.5 in that medical researchers and doctors are slowly figuring out some limited second order effects, like "X medicine with Y gene" or "X medicine with Y medicine" can have good or bad effects.

We're certainly not talking about 3rd order effects.. We have the math, we have the statistics, but it's just hard maths and stats.

Re: Study: Electroshock therapy more successful for depression than ketamine

#74
It's really dissapointingly seeing the comments section do exactly what the article tries to avoid. There seems to be so much lack of understanding for the process of prescribing treatment for depression, and overreliance on endless anecdotes or other singular data points, directly at the antithesis of the study:

> “Every single study directly reports ECT works better than ketamine. But _people are still skeptical of ECT, perhaps because of stigma_,” Rhee says, or negative depictions in films such as “One Flew Over the Cuckoo’s Nest” and shows such as “Stranger Things.” “_We need to improve public awareness of ECT for treatment-resistant depression_.”

If we read the article carefully, we can see that the headline (as all headlines are) is lacking in nuance:

> Most people diagnosed with depression are offered an _oral antidepressant (in combination with psychotherapy) as a first-line treatment option_. But _if oral antidepressants don’t help, or if the person is at imminent risk of hurting themselves_, there are other, more rapid treatment options: ECT, and more recently ketamine or esketamine.

Firstly, oral antidepressants and psychotherapy are still the firstly line of defence, and for the majority of people enough. As it is, ketamine or esketamine is nowhere near close - has nowhere near enough evidence and longitudinal studies - to replace SSRIs and psychotherapy as the first line. Unfortunately modern medicine isn't advanced enough to fully understand what's going on with oral antidepressants (we have theories, but the majority evidence is simply statistics), let alone (es) ketamine and ECT. As a result, if oral antidepressants are not effective it can often be difficult to effectively prescribe treatment. Naturally a consequence of this is increased risk, from procedures that may not have much if any benifits, not even including the very real chances of a misdiagnosis!

If we look at the cited paper's abstract, the message is even more clear

> Question: Is ketamine as effective as electroconvulsive therapy (ECT) in patients with _major depressive episode_?

> Findings: This systematic review and meta-analysis of 6 trials with 340 patients suggests that ECT may be superior to ketamine in improving depression severity. Findings also suggest that ketamine and ECT each have unique adverse effect profiles.

> The overall pooled SMD for depression symptoms for ECT when compared with ketamine was −0.69 (95% CI, −0.89 to −0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity.

> Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms).

> Meaning: Although ECT may be more efficacious than ketamine in the acute phase, _treatment options should be individualized and patient-centered, considering different adverse effect profiles and patient preferences._

Both (Es)Ketamine and ECT are useful and sometimes literally life saving therapies for those with treatment resistant depression. Like any treatment some respond effectively and may never have to undergo future treatment whilst others may require constant support. The stigma around ECT and the uninformed experience and use of anecdotes is dangerous, and ignores the reality that there are no good answers, at least with our current medical knowledge.

I would advise not drawing any conclusions from limited evidence, and if they want to see more personal anecdotes explore both the positive and negative comments at /r/ECT and /r/TherapeuticKetamine

Re: Study: Electroshock therapy more successful for depression than ketamine

#75
post #38
post #23

My friend figured out for herself, when she was in her 30's, that she's a poor methylator who can't turn the food fortification folic acid into a usable form of Vitamin B-9. She once told me that adding L-Methylfolate to her routine was like flipping a switch from "depressed" to "not-depressed". But the doctors had already decided she was being "stabilized" by the anti-psychotic prescriptions they forced on her, so t…

> ECT should be retired from use. I heard once that brain damage causes the brain to increase production of the steroid allopregnanolone. The beneficial effect of the SSRI's seem to also be related to increased allopregnanolone, NOT to boosting serotonin levels. That's a fascinating insight. Recent medical research implicates neuroinflammation in the pathogenesis of depression [0][1]. Steroids generally have anti-inf…

There's studies from the 80's & 90's showing direct destruction of neurons in mice and chimpanzees with depression like symptoms. Depression it seems literally eats away at the brain, at least in mammals, likely due to inflammation.

What's perplexed me is why this mechanism would occur in evolutionary terms, or if it's really just a byproduct.

Re: Study: Electroshock therapy more successful for depression than ketamine

#76
"Relapse rates after ECT are similar to those in resistant depression treated with antidepressants (37% after six months) and are a function of the illness, reinforcing need to continue with antidepressants, ECT, or both after a successful acute course of ECT.37 Emerging evidence suggests maintenance ECT to prevent relapse.38"

https://www.bmj.com/content/364/bmj.k5233

This article is arguing ECT as acute treatment for resistant depression. In most, if not all, cases a patient would become eligible for ketamine treatment at the same time if not sooner than ECT. Memory loss directly due to ECT is the reason most people are strongly against using it. Treatment options are based on minimizing risks, not guaranteeing success. Unless ketamine is contraindicated, it will always be a safer treatment than ECT.

Re: Study: Electroshock therapy more successful for depression than ketamine

#77
post #41

Earlier quoted context omitted.

Interesting information... it prompted me to do more research. According to wikipedia, Vitamin B-9 is broken down by our bodies into a family of compounds called "THF", which: 1. Help synthesize DNA, 2. Help repair/modify DNA, 3. Help create the amino acid "Methionine", which is a precursor to other amino acids, and is thus important for the synthesis of many proteins inside the body, 4. Activate Vitamin B12. A defic…

> One of these days, when I have enough free time, I want to develop a particle-level simulation of the human body, so that medical students, doctors, and curious laymen can see these processes in action on their personal computers. Likely you wouldn't need/want a particle level simulation, but a kinetics level model. Just with kinetics you could draw simulations of "particle concentrations" or other fun things to sh…

Sadly even a kinetics level simulation for anything remotely complex is far beyond what current compute is capable of. Even simplified models of basic biological processes are immensity complex, and still potentially incomplete. Just as neural networks do not even attempt to reach the level of molecules, (practical) models must necessarily exist at a much higher abstraction.

Although alphafold is a breakthrough, this is less optimisation, more chaos theory.

Re: Study: Electroshock therapy more successful for depression than ketamine

#78

Earlier quoted context omitted.

"Not feeling incredibly depressed."

Or, more accurately, not reporting to the researchers that you're feeling incredibly depressed.

The same skepticism can be applied to any study, depression treatment or otherwise. Practically, self reporting is highly effective and well correlated with effects, especially for depression.

Re: Study: Electroshock therapy more successful for depression than ketamine

#79

Earlier quoted context omitted.

The musician Townes Van Zandt underwent ECT and the loss of his memory haunted him his whole (very tragic) life. It's well-known how deep of an impact that had on him, and not for the better. As if the often pleasant, often interesting, often terrifying yet short term and proven harmless side-effects of Ketamine can even compare to the ECT! I would like to see how _much_ better ECT is, given all the factors. Addition…

A single data point may be a interesting, but strong evidence it does not make. Nor does speculating about a doctors caution without citations. Ketamine in recreational use has equally documented side effects, some quite severe. Extreme circumstances that have caused irreparable damage are rare, but not unheard of. There are also numerous other anecdotes from people that have undergone numerous session of ECT with mi…

What sort of side effects are we talking about?

As far as I know, bladder damage is the only actual physical effect of ket

Re: Study: Electroshock therapy more successful for depression than ketamine

#80
post #65
post #48

Earlier quoted context omitted.

Curious what you mean by “particle level”? Like simulating every molecule in the body?

At this time, I mean every hormone and protein flowing in the bloodstream, along with the state of every single cell. Essentially, enough detail to get a list of symptoms and bodily sensations, and predict the outcome of any potential blood test or urinalysis. Or, alternatively, enough detail to take the results of a blood test/urinalysis, and predict the state of every single tissue in the body.

It's something way beyond our current capabilities.

There's some interesting work on "organs on a chip" e.g. arrays of microfluidic cell cultures that allows some experimentation on a combination of a few types of tissue modeling an organ or some aspect of it, but even that's already pushing the state of art and not fully mature at the moment; doing something similar for many (much less all or most) organs is something that doesn't work yet; and these "organs on a chip" are useful because pure simulation is even less mature and is unable to do what these cell cultures can.

The goal you state is interesting, relevant, and potentially achievable, but it's still some decades away.

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